In the United States, approximately 150,000 patients are diagnosed with colorectal cancer each year. About 20% of these patients have metastatic deposits of colorectal cancer in the liver only at the time of diagnosis or develop such metastases during the course of their illness. In the absence of treatment, the prognosis for patients with hepatic colorectal metastases is dismal, with 5-year survival rates of 3% or less. There is now evidence that resection of such metastases can improve the prognosis. Although liver resection is not the primary treatment for most patients with hepatic colorectal metastases, appropriate liver resection is the standard of care for treatment of patients with isolated hepatic colorectal metastases. The majority of patients experience recurrence following hepatic resection of colorectal metastases. Patients at high risk for recurrence after hepatic resection are those who present with multiple hepatic metastases (vs. single metastases), large metastatic tumors (>5 cm), a high CEA serum concentration (>200 ng/mL), a node-positive primary colorectal cancer, or synchronous tumors (primary colorectal cancer and hepatic colorectal metastases). A treatment that reduced or eliminated recurrence after hepatic resection would be highly desirable.
The notion that tissue inflammation and tumor growth are intricately associated phenomena is relatively old, but the cell types and signaling intermediates that define this interrelationship are only beginning to be identified, as are the potential targets for therapeutic intervention. Most studies have focused on elucidating how chronic inflammation promotes the progression of pre-malignant to malignant lesions. Previous work has shown that the outgrowth of late stage tumors (colorectal liver metastases) is stimulated by inflammation and necrosis of liver tissue following ischemia/reperfusion (I/R)(see Hepatology 2005, 42, 165-175; and, Br. J. Surg. 2006, 93, 1015-1022). Unfortunately, the mechanisms underlying the accelerated outgrowth of inflammation-associated late-stage metastatic tumors are unknown. Thus, the development of an effective treatment that suppresses surgery-induced inflammation-associated tumor growth is desirable.